血管内皮生长因子在恶性嗜铬细胞瘤中的表达及与MVD的关系

Expression of vascular endothelial growth factor(VEGF) in malignant pheochromocytomas and the relationship between VEGF and microvessel density

目的通过检测血管内皮生长因子(VEGF)、微血管密度(MVD)在良、恶性嗜铬细胞瘤中的表达情况,探讨VEGF能否成为预判恶性嗜铬细胞瘤的指标,并阐明其与MVD间的关系。方法选取1986年10月-2006年8月住院经手术治疗,且具有完整的临床、病理和随访资料的嗜铬细胞瘤患者存档石蜡标本38例,其中良性嗜铬细胞瘤21例,恶性嗜铬细胞瘤17例。恶性嗜铬细胞瘤组中首次手术确诊为嗜铬细胞瘤后随访4-155个月;良性嗜铬细胞瘤组中首次手术确诊为嗜铬细胞瘤后随访69-240个月。另取20例因良性肾疾患行肾切除时获取的同侧正常肾上腺组织作为对照组。采用免疫组织化学技术,检测良、恶性嗜铬细胞瘤及20例正常肾上腺髓质组织中VEGF的表达情况及CD34标记的MVD表达情况。结果VEGF在恶性嗜铬细胞瘤中呈高表达,阳性率为82.40%,在良性嗜铬细胞瘤和正常肾上腺髓质组织中的阳性率分别为23.80%、5.00%,VEGF在恶性嗜铬细胞瘤中的表达与在良性嗜铬细胞瘤和正常肾上腺髓质组织中的表达有显著性差异(P<0.05),而在良性嗜铬细胞瘤和正常肾上腺髓质组织中的表达没有显著性差异(P>0.05)。MVD在恶性嗜铬细胞瘤中表达最高(36.41±13.00),良性嗜铬细胞瘤中次之(21.43±8.05),正常肾上腺髓质组织中表达最少(13.36±4.34),两两之间比较有显著性差异(P<0.05)。在嗜铬细胞瘤中VEGF的表达与MVD呈正相关。结论VEGF有望成为预判恶性嗜铬细胞瘤的一项指标。VEGF在恶性嗜铬细胞瘤中的表达与MVD呈正相关,提示微血管的形成与VEGF的调控有关,MVD增高是恶性嗜铬细胞瘤发生侵袭和远处转移的基础。

Objective To detect the expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） in benign and malignant pheochromocytomas respectively and to analyse the value of VEGF as marker for malignant pheoehromocytomas; meanwhile, to investigate the relationship between VEGF and MVD. Methods Tissue specimens were obtained at operations performed in Ruijin Hospital from 1986-2006. There were 38 pheochromocytomas （including 21 benign and 17 malignant） and the clinical and pathological data were available. The malignant group follow-up time ranged from 4 to 155 months. The benign group follow-up time ranged from 69 to 240 months. Normal adrenal glands were from 20 patients undergoing nephrectomy for benign renal tumor. Immunohistochemical technology was performed to detect the VEGF and MVD（marked with CD34） in all patients. Results Strong VEGF expression was found in malignant pheochromocytomas （82.40%）, whereas weak expression in benign pheochromocytomas （23. 80%） and in normal adrenal medulla （5. 00%） respectively. There was statistical difference between the malignant group and benign group, also between the malignant group and normal adrenal medulla group （P 〈 0.05）. However, there was no statistical difference between the benign group and normal adrenal medulla group （P 〈 0.05 ）. High MVD expression was found in malignant pheochromocytomas （36.41 ± 13.00）, whereas low expression in benign pheochromocytomas （21.43 ± 8.05） and in normal adrenal medulla （13.36 ±4.34）. There was statistical difference between the groups （P〈0.05）. There was positive relationship between VEGF and MVD in pheoehromocytomas. Conclusion VEGF may become the predicton marker for malignant pheochromocytoma. There is positive relationship between VEGF and MVD in malignant pheochromocytoma and the phenomena indicate the formation of mierovessel is regulated by VEGF. Increasing MVD is the basis for invasion and metastases in malignant pheochromocytoma.